A Phase 1/1b Study of MEDI3726 in Adults Subjects With Metastatic Castration Resistant Prostate Cancer

Metastatic Castration Resistant Prostate Cancer Clinical Trial

— MEDI3726  

Official title:

A Phase 1/1b Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI3726 in Subjects With Metastatic Castration Resistant Prostate Cancer Who Have Received Prior Treatment With Abiraterone or Enzalutamide.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02991911
• Other study ID #: D9320C00001
• Status: Completed
• Phase: Phase 1
• Start date: January 6, 2017
• Est. completion date: September 30, 2019

Study information

• Verified date: January 2020
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety and tolerability, describe the dose-limiting toxicities (DLTs), and determine the maximum tolerated dose (MTD) or maximum administered dose (MAD [in the absence of establishing the MTD]) for single agent MEDI3726 in subjects with mCRPC who have received prior treatment with abiraterone or enzalutamide, with or without a prior taxane-based chemotherapy in the mCRPC setting.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: September 30, 2019
• Est. primary completion date: September 30, 2019
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• Age = 18 years at the time of screening.

• Histologically confirmed diagnosis of metastatic castration-resistant prostate adenocarcinoma (mCRPC).

• Documented PD in subjects with mCRPC as assessed by the Investigator and defined by at least one of the following according to the PCWG3 criteria:

1. Radiographic progression.

2. PSA progression.

• Prior exposure to abiraterone or enzalutamide of at least 12 weeks in the mCRPC setting.

NOTE: Subjects who have received both abiraterone and enzalutamide in the mCRPC setting are eligible.

• In dose escalation: Prior taxane-based chemotherapy in the mCRPC setting is:

1. Required for Arm A.

2. Excluded for Arm B.

3. Optional for Arm C.

Exclusion Criteria:

• Subjects with neuroendocrine, neuroendocrine differentiation and/or small cell prostate cancer.

• The subject has received any conventional or investigational anti-cancer treatment within 21 days before the first dose of investigational product, with the following modifications:

1. At least 14 days before the first dose of investigational product since completion of treatment with abiraterone or enzalutamide

2. At least 14 days before the first dose of investigational product since completion of prior taxane-based chemotherapy

3. At least 28 days before the first dose of investigational product since completion of treatment with Radium-223.

4. At least 42 days before the first dose of investigational product since completion of prior bicalutamide and nilutamide treatment.

NOTE: An LHRH agonist or antagonist required for ongoing testosterone suppression will be permitted if Inclusion Criterion is satisfied.

• Prior exposure to PSMA-directed therapies.

• Subjects with previous radiotherapy for the treatment of unresectable, locally advanced or metastatic prostate cancer are excluded if:

1. More than 25% of marrow-bearing bone has been irradiated.

2. The last fraction of radiotherapy has been administered within approximately 2 weeks prior to the first dose of investigational product.

• Brain metastases that are untreated, symptomatic, or require therapy to control symptoms; or any radiation, surgery, or other therapy to control symptoms from brain metastases within 2 months prior to the first dose of investigational product.

• Subjects with known history of peripheral vasculopathies including, but not limited to, macro and microangiopathies secondary to diabetes, peripheral arteriopathy of any cause, intermittent claudication, repeated and/or non-healing ulcers of any cause.

Related Conditions & MeSH terms

• Metastatic Castration Resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

Biological:
• MEDI3726 Post-Chemo
Single agent MEDI3726 after abiraterone or enzalutatmide, with a prior taxane-based chemotherapy in the mCRPC setting
• MEDI3726 Pre-Chemo
Single agent MEDI3726 after abiraterone or enzalutatmide, without a prior taxane-based chemotherapy in the mCRPC setting
• MEDI3726 & Enzalutamide Combo
MEDI3726 in combination with Enzalutatmide after prior treatment with abiraterone, with or without a prior taxane-based chemotherapy in the mCRPC setting

Locations

Country	Name	City	State
Switzerland	Research Site	Chur
United Kingdom	Research Site	London
United States	Research Site	New Haven	Connecticut
United States	Research Site	Norfolk	Virginia
United States	Research Site	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

United States,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of adverse events (AEs)	Safety Endpoint	From time of informed consent through 90 days after last dose of MEDI3726
Primary	Occurrence of serious adverse events (SAEs)	Safety Endpoint	From time of informed consent through 90 days after last dose of MEDI3726
Primary	Occurrence of dose-limiting toxicities (DLTs)	Safety Endpoint	From time of first dose through 21 days after first dose of MEDI3726
Primary	Number of patients with changes in laboratory parameters from baseline	Safety Endpoint	From time of informed consent through 90 days after last dose of MEDI3726
Primary	Number of patients with changes in vital signs from baseline	Safety Endpoint	From time of informed consent through 21 days after last dose of MEDI3726
Primary	Number of patients with changes in electrocardiogram (ECG) results from baseline	Safety Endpoint	From time of informed consent through 21 days after last dose of MEDI3726
Secondary	Response Evaluation Criteria in Solid Tumors (RECIST) response	Response according to RECIST version 1.1	From time of informed consent through 90 days after last dose of MEDI3726
Secondary	PSA50 response	Reduction in PSA level of 50% (PSA50) or more compared with baseline	From time of fist dose through at least 12 weeks after first dose of MEDI3726
Secondary	Circulating Tumor Cell (CTC) response	Conversion in the CTC count defined as a reduction from = 5 cells/7.5 mL blood to < 5 cells/7.5 mL blood with a confirmatory assessment at least 4 weeks later	From time of informed consent through 90 days after last dose of MEDI3726
Secondary	Safety and tolerability of MEDI3726 in combination with Enzalutamide	Measured by occurrence of AEs, SAEs, DLTs and number of patients with changes in laboratory parameters, vital signs, and ECG results from baseline	From time of informed consent through 90 days after last dose of MEDI3726 with enzalutamide
Secondary	MEDI3726 plasma concentrations for pharmacokinetics (PK)		From time of informed consent through 90 days after last dose of MEDI3726
Secondary	MEDI3726 maximum observed concentration for PK		From time of informed consent through 90 days after last dose of MEDI3726
Secondary	MEDI3726 area under the concentration-time curve for PK		From time of informed consent through 90 days after last dose of MEDI3726
Secondary	MEDI3726 clearance for PK		From time of informed consent through 90 days after last dose of MEDI3726
Secondary	MEDI3726 terminal half-life for PK		From time of informed consent through 90 days after last dose of MEDI3726
Secondary	Number and percentage of subjects who develop anti-drug antibodies (ADAs)	To determine the immunogenicity of MEDI3726	From time of informed consent through 90 days after last dose of MEDI3726